2262P - Baseline-informed versus tumor-agnostic minimal residual disease (MRD) concordance study in patients with HER2+ gastroesophageal adenocarcinoma patients

Background

Current clinical paradigms are reliant on radiographic monitoring of disease to assess treatment response. However, this approach has some limitations including interval nature of imaging modalities and patients can clinically deteriorate prior to formally documenting therapy resistance. Hence, novel techniques such as longitudinal monitoring circulating tumor DNA (ctDNA) to assess therapy related response in real time are important to investigate.

Methods

To assess changes in disease burden with therapy, we profiled circulating tumor DNA (ctDNA) from longitudinal patient blood plasma using PredicineBEACON personalized minimal residual disease (MRD) assay and PredicineALERT, a tumor-agnostic MRD assay that measures cancer-related methylation patterns without personalization. Nineteen longitudinal plasma samples from 2 HER2+ gastroesophageal cancer (GEC) patients were tested using baseline-informed and tumor-agnostic MRD assays.

Results

Patient 1 demonstrated a similar trend of molecular dynamics and turning points of tumor response to therapy across 9 time points between the two MRD assays. Although the overall trends between the two assays were concordant for the second patient, some time points showed differential dynamics of changes in circulating levels of specific mutations compared to overall methylation profiling. An uptick levels of ctDNA after initial response preceeded radiographic progression using either approaches. Overall, in this ongoing study of the initial 2 cancer patients using 19 longitudinal blood samples, both PredicineALERT and PredicineBEACON assays demonstrated the trend of molecular dynamics and identified the similar turning points of tumor response during therapy.

Conclusions

Both tumor informed mutation based and tumor agnostic mehtylation based ctDNA approaches demonstrate clinical potential to monitor disease evolution and identify resistance prior to radiographic progression. Further study of such approaches to identify pre-radiographic molecular progression is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Du, G. Bonora, S. Jia: Financial Interests, Personal, Full or part-time Employment: Predicine. H. Singh: Other, Personal and Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck, DewPoint therapeutics. P.C. Enzinger: Financial Interests, Advisory Role: ALX oncology, Arcus Bioscience, Astellas, AstraZeneca, Blueprint medicine, BMS, Chimeric Therapeutics, Celgene, Coherus, Daiichi Sankyo, Five Prime, IDEAYA, Istari, Legend, Lilly, Loxo, Merck, Novartis, Ono, Servier, Taiho, Takeda, Turning Point Therapeutics, Xencor, Zymeworks.